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Biomedical subjects

R L Thompson

Publications and source records attributed to R L Thompson.

At least 55 records · Page 3Linked to original sources
PubMed1996

The region of the herpes simplex virus type 1 LAT gene that is colinear with the ICP34.5 gene is not involved in spontaneous reactivation.

The goal of this report was to determine if the region of the LAT gene that is colinear with ICP34.5 (kb 6.2 to 7.1 of LAT) is involved in spontaneous reactivation of herpes simplex virus type 1. We inserted one copy of the ICP34.5 gene into the unique long region of a herpes simplex virus type 1 (strain McKrae) mutant lacking both copies of ICP34.5 (one in each viral long repeat) and the corresponding 917-nucleotide colinear portion of LAT (kb 6.2 to 7.1). Rabbits were ocularly infected with this mutant, and spontaneous reactivation relative to that for the wild-type virus and the original mutant was measured. As we previously reported, the original ICP34.5-deleted virus (d34.5) was significantly impaired for spontaneous reactivation and virulence (G. C. Perng, R. L. Thompson, N. M. Sawtell, W. E. Taylor, S. M. Slanina, H. Ghiasi, R. Kaiwar, A. B. Nesburn, and S. L. Wechsler, J. Virol. 69:3033-3041, 1995). In contrast, we report here that restoration of one copy of ICP34.5 at a distant location completely restored the wild-type level of in vivo spontaneous reactivation, despite retention of the deletion in LAT (spontaneous reactivation rate = 0.3 to 1.4% for the ICP34.5 deletion mutant, 7.7 to 19.6% for the wild type, and 9 to 16.1% for virus with one copy of ICP34.5). Thus, the 917-nucleotide region of LAT from kb 6.2 to 7.1 was not involved in the LAT function required for wild-type spontaneous reactivation. We also found that restoration of a single ICP34.5 gene in a novel location did not restore wild-type virulence (rabbit death rate = 0% [0 of 15] for the original ICP34.5 deletion mutant, 8% [2 of 24] for the single-copy IPC34.5 virus, and 52% [14 of 27] for wild-type virus; P < 0.001 for one versus two copies of ICP34.5). It is likely that either two gene doses of ICP34.5 or its location in the long repeat is essential for full functionality of ICP34.5's virulence function. Furthermore, the ability of the single-copy ICP34.5 virus to reactivate at wild-type levels despite being significantly less virulent than wild-type virus separates the spontaneous reactivation phenotype from the virulence phenotype.

Animals↗
PubMed1996

Wet-cold exposure and hypothermia: thermal and metabolic responses to prolonged exercise in rain.

Simulated conditions of hiking in rain, wind, and cold, without protective rainwear, were used to investigate wet-cold hypothermia in 18 male subjects. Thermal, metabolic, and motor responses were monitored during an attempted 5-h walk (5.1 km/h) at 5 degrees C, with continuous exposure to rain (7.4 cm/h) and wind (8.0 km/h) over the final 4 h. The majority of subjects (11) could not complete the protocol because of intolerance of wet-cold conditions during the last 2 h. Therefore, data from 5 subjects who completed the protocol in rain and control conditions were used to describe the general pattern of response. During the 1st h of walking, core temperature rose 1 degree C to 38.1 degrees C. The subsequent 2 h of rain caused substantial cold stress, indicated by a 40% increase in heat production due to shivering and significant loss of strength and manual dexterity. However, core temperature only decreased to 37.1 degrees C, merely eliminating the initial exercise hyperthermia. Over the last 2 h of rain, core temperature remained relatively stable at 36.8 degrees C, decreasing slightly to 36.4 degrees C by 5 h. Two other subjects developed significant hypothermia (35 degrees C). One demonstrated fatigue of shivering after 2.5 h of rain, confirming the exhaustion hypothesis of wet-cold hypothermia. The older cooled rapidly when he failed to maintain the walking pace. We conclude that if a person can tolerate the intense discomfort of prolonged wet-cold exposure, he or she has the potential to resist significant core hypothermia for at least 4 h of walking under the conditions of this experiment. Exceptions to this generalization occur, making exposure of < 4 h a hypothermia risk for some individuals. Exposures > 4 h would involve increasing probability of rapid decline into hypothermia, associated with exhaustion of shivering and exercise heat production.

Adult↗
PubMed1996

Infectious rates of central venous pressure catheters: comparison between newly placed catheters and those that have been changed.

OBJECTIVE: To analyze the rate of infection of de novo, guidewire exchanged, and new site replacement catheters in a cohort of patients in whom catheters were changed on the basis of the clinical discretion of the attending physicians. DESIGN: We conducted an observational cohort study in catheterized patients in the intensive-care unit (ICU). MATERIAL AND METHODS: ICU patients admitted between Jan. 1, 1991, and Dec.31, 1992, were eligible for enrollment in the study. Catheter care, replacement, and duration were prospectively documented. Catheter-related infection was prospectively evaluated. Rates of catheter-related infection were determined for de novo, guidewire exchanged, and new site replacement catheters and analyzed relative to the duration of placement of individual catheters and the total duration of central venous catheterization for a specific patient. RESULTS: Fifty catheter-related infections developed in 2,470 patients. When the rate of catheter-associated infection was determined for each type of catheterization, de novo catheters had a lower observed rate of infection than either replacement type (P < or = 0.0001). After controlling for the effect of time, we found that the rate of catheter-related infections associated with a de novo catheter was less than the rate in guidewire exchanged catheters (P = 0.035). Rates of infection were similar between guidewire exchanged catheters and catheters replaced to a new site. CONCLUSION: In a population of ICU patients in whom catheter change was governed by clinical judgement, no differences were noted between the observed rates of infection of new site replacement catheters and guidewire exchange catheters.

Adult↗
PubMed1995

Dietary change after smoking cessation: a prospective study.

A population sample of 375 men and women cigarette smokers were recruited to take part in a prospective study of smoking cessation to test the hypothesis that stopping smoking is associated with an increased consumption of the essential fatty acid linoleic acid, which explains the concomitant reduction in risk of coronary heart disease. Diet was assessed using a 10 d weighed record in 301 smokers at baseline, 153 at 4-month follow-up, of whom twenty-six had quit smoking, and 122 at 1-year follow-up, of whom twenty had quit. Compared with continuing smokers, those who had quit at the 4-month follow-up (mean 10 and 13 weeks for men and women respectively) had statistically significant increases in body weight (5%), energy intake (13%), total dietary fat (24%), all specific types of dietary fat (26% polyunsaturated fat, 26% linoleic acid, 30% eicosapentaenoic acid, 23% monounsaturated fat and 22% saturated fat) and vitamin E intake (19%). The foods which appeared to contribute to increases in energy and fat intakes at the 4-month follow-up were vegetable oils and polyunsaturated margarines, processed meats and meat pies. By follow-up at 1 year (mean time since quitting 31 and 41 weeks for men and women respectively) there were no detectable differences in energy and total fat intakes. However, intakes of eicosapentaenoic acid and pteroylglutamate (folate) were statistically significantly higher in the quitters compared with the continuing smokers (37% for eicosapentaenoic acid and 16% for folate). We conclude that the short-term increase in dietary intake of linoleic acid, which is not sustained by 1 year, cannot explain the reduction in risk of coronary disease following smoking cessation.

Adult↗
PubMed1995

Development of a scoring system to judge the scientific quality of information from case-control and cohort studies of nutrition and disease.

A scoring system was developed to help judge the scientific quality of observational epidemiologic studies linking diet with risk of cancer. The scoring system was developed from key headings used in developing research protocols and included questions under headings: three for case-control studies (dietary assessment, recruitment of subjects, and analysis) and four for cohort studies (dietary assessment, definition of cohort, ascertainment, and analysis). Points were awarded for questions in each section, and a total score was derived. Interobserver variation was assessed for five case-controls and five cohort studies for 13 observers: 1 observer repeated the assessment of each paper. Absolute scores and ranking within observer were assessed. There was good agreement between observers in the ranking of studies. Papers that scored higher presented sufficient detail to enable the questions in the scoring system to be answered more easily. For some studies, the information required was either not collected or, if it was collected, not presented. In either case, the frequent lack of information available to judge papers raises questions about the editorial policy and review process of journals publishing dietary studies as much as it does about the scoring system. Applying the scoring system to a review of meat and cancer risk suggested that, taking the score into account, from what seemed like a large literature, there were relatively few studies that scored well (defined as a score > 65%), but these studies tended to provide more consistent information.

Case-Control Studies↗
PubMed1995

Oleoresin capsicum (pepper) spray and "in-custody deaths".

Increasing use of oleoresin capsicum (OC) spray devices (i.e., pepper spray, pepper mace, OC, capsaicin) by law enforcement agencies as a means of sublethal force to control suspects has brought into question whether exposure to this noxious irritant (capsaicin) can cause or contribute to unexpected in-custody deaths. Capsaicin stimulates nociceptors in exposed mucous membranes to produce intense pain, particularly involving the conjunctiva, and generates systemic physiologic and behavioral responses consonant with such extreme discomfort. We describe two cases of in-custody death, both associated temporally with the use of pepper spray, to illustrate salient investigative considerations. As with any other in-custody death, a thorough autopsy and toxicologic analysis, coupled with evaluation of the premortem chain of events, postexposure symptomatology, and the extent of natural disease processes, will help to reveal the role of oleoresin capsicum spray as unrelated, contributory, or causative.

Adult↗
PubMed1995

An avirulent ICP34.5 deletion mutant of herpes simplex virus type 1 is capable of in vivo spontaneous reactivation.

The herpes simplex virus type 1 (HSV-1) ICP34.5 gene is a neurovirulence gene in mice. In addition, some ICP34.5 mutants have been reported to have a reduced efficiency of induced reactivation as measured by in vitro explantation of latently infected mouse ganglia. However, since spontaneous reactivation is almost nonexistent in mice, nothing has been reported on the effect of ICP34.5 mutants on spontaneous reactivation in vivo. To examine this, we have deleted both copies of the ICP34.5 neurovirulence gene from a strain of HSV-1 (McKrae) that has a high spontaneous reactivation rate in rabbits and used this mutant to infect rabbit eyes. All rabbits infected with the ICP34.5 mutant virus (d34.5) survived, even at challenge doses greater than 4 x 10(7) PFU per eye. In contrast, a 200-fold-lower challenge dose of 2 x 10(5) PFU per eye was lethal for approximately 50% of rabbits infected with either the wild-type McKrae parental virus or a rescued ICP34.5 mutant in which both copies of the ICP34.5 gene were restored. In mice, the 50% lethal dose of the ICP34.5 mutant was over 10(6) PFU, compared with a value of less than 10 PFU for the rescued virus. The ICP34.5 mutant was restricted for replication in rabbit and mouse eyes and mouse trigeminal ganglia in vivo. The spontaneous reactivation rate in rabbits for the mutant was 1.4% as determined by culturing tear films for the presence of reactivated virus. This was more than 10-fold lower than the spontaneous reactivation rate determined for the rescued virus (19.6%) and was highly significant (P < 0.0001, Fisher exact test). Southern analysis confirmed that the reactivated virus retained both copies of the ICP34.5 deletion. Thus, this report demonstrates that (i) the ICP34.5 gene, known to be a neurovirulence gene in mice, is also important for virulence in rabbits and (ii) in vivo spontaneous reactivation of HSV-1 in the rabbit ocular model, although reduced, can occur in the absence of the ICP34.5 gene.

Animals↗
PubMed1995

Evolution of rifampin resistance in human immunodeficiency virus-associated tuberculosis.

Acquired rifampin resistance without preexisting isoniazid resistance is highly unusual in patients with tuberculosis. The purpose of this report is to describe and characterize that unusual pattern of acquired drug resistance in three patients with human immunodeficiency virus (HIV) infection. The patients originally had Mycobacterium tuberculosis strains that were susceptible to isoniazid and rifampin. During treatment in two patients and after completion of therapy in the remaining one, each patient developed active, rifampin-resistant, isoniazid-susceptible tuberculosis. One patient subsequently developed isoniazid resistance also. Studies on patients' M. tuberculosis isolates using IS6110 restriction fragment length polymorphism typing and rpoB gene sequencing indicated that rifampin resistance in each patient arose during therapy by an rpoB gene mutation in the original M. tuberculosis isolate. Detection of this unusual drug-resistance phenotype in three patients with HIV infection suggests that acquired rifampin resistance is somehow associated with co-infection due to HIV and tuberculosis.

AIDS-Related Opportunistic Infections↗
PubMed1994

ICP34.5 mutants of herpes simplex virus type 1 strain 17syn+ are attenuated for neurovirulence in mice and for replication in confluent primary mouse embryo cell cultures.

In a recent report, the neurovirulence of herpes simplex virus type 1 (HSV-1) was mapped to the ICP34.5 gene (J. Chou, E. R. Kern, R. J. Whitley, and B. Roizman, Science 250:1262-1266, 1990). In this report, specific mutations within ICP34.5 were constructed in HSV-1 strain 17syn+ to determine the effects of these mutations in a fully neurovirulent isolate. It was found that termination of the ICP34.5 gene after the N-terminal 30 amino acids resulted in a mutant, 17termA, which was 25- to 90-fold reduced in neurovirulence. This reduction of neurovirulence was associated with restricted replication of the mutant virus in mouse brain. The reduced replication phenotype was also evident in the trigeminal and dorsal root ganglia following inoculation at the periphery. 17termA was capable of replicating with wild-type kinetics in mouse footpads, and therefore the restriction seen in neural tissues was not due to a generalized replication defect in mouse cells. Significantly, replication of the mutant was also restricted in the mouse cornea in vivo and in confluent primary mouse embryo cells and mouse 10T1/2 cells in vitro. However, 17termA replicated with much greater efficiency in subconfluent mouse embryo cells, suggesting that the physiological state of the cell may be an important factor for productive replication of this mutant. Restoration of the ICP34.5 gene to the mutant resulted in a virus which displayed wild-type neurovirulence and replication kinetics in all cells and tissues tested.

Animals↗
PubMed1994

Mutations in accessory DNA replicating functions alter the relative mutation frequency of herpes simplex virus type 1 strains in cultured murine cells.

The contribution of the herpes simplex virus type 1 (HSV-1)-encoded uracil DNA glycosylase (UNG), thymidine kinase (TK), and dUTPase to the relative mutant frequency (RMF) of the virus in cultured murine cells was examined. A panel of HSV-1 mutants that lacked singly or doubly the UNG, TK, or dUTPase activity were generated by disruption of the enzyme coding regions with the Escherichia coli beta-galactosidase (beta-gal) gene in strain 17syn+. To establish a baseline RMF of strain 17syn+, the beta-gal gene was inserted into the UL3 locus. In all of the viruses, the beta-gal insert served as a phenotypic marker of RMF. A mutant plaque was identified by the lack of beta-gal activity and, in selected cases, positive in situ hybridization for beta-gal sequences. Replication kinetics in NIH 3T3 cells demonstrated that all of the mutants replicated efficiently, generating stocks with equivalent titers. Two independently generated UL3-beta-gal viruses were examined and established a baseline RMF of approximately 0.5% in both NIH 3T3 and LM TK- cells. Loss of dUTPase activity resulted in viruses with fivefold-increased RMFs, indicating that the HSV-1 dUTPase has an antimutator function. The RMF observed for the tk- viruses was reduced as much as 40-fold (RMF of 0.02%), suggesting that the viral TK is a mutator activity. The RMF of two independent UNG- viruses showed no significant difference from the baseline RMF in limited passage; however, following successive passage, the data suggested that UNG activity serves as an antimutator. These results have implications for the natural history of HSV and the development of antiviral therapies.

3T3 Cells↗
PubMed1994

Evidence that the herpes simplex virus type 1 uracil DNA glycosylase is required for efficient viral replication and latency in the murine nervous system.

Herpes simplex virus (HSV) encodes a uracil DNA glycosylase (UNG; UL2), which has been shown to be dispensable for normal replication of HSV-1 in cultured cells (J. Mullaney, H.W. Moss, and D.J. McGeoch, J. Gen. Virol. 70:449-454, 1989). In adult neurons, UNG activity is undetectable (F. Focher, P. Mazzarello, A. Verri, U. Hubscher, and S. Spadari, Mutat. Res. 237:65-73, 1990), suggesting that the HSV-1 UNG may play an important role in viral replication in neurons acutely and/or following reactivation. To examine the contribution of the HSV-1 UNG in vivo, two independent strain 17 Syn+ Ung- mutants, designated uB1 and uB2, were examined in a mouse model of herpetic disease. Following direct intracranial inoculation, both mutants exhibited a 10-fold reduction in neurovirulence compared with the parental strain 17 Syn+. Inoculations by a peripheral route demonstrated that the Ung- mutants were at least 100,000-fold less neuroinvasive than 17 Syn+. Replication kinetics in vivo demonstrated that uB1 and uB2 replicated less well in both the mouse peripheral and central nervous systems. Latency was established by both of the mutants in 100% of the animals examined. Following transient hyperthermia, however, the frequency of reactivation of the mutants in vivo was dramatically reduced. Restoration of the UNG locus resulted in full neurovirulence, neuroinvasiveness, and the ability to reactivate in vivo. These findings suggest that the HSV-1 UNG plays an important role during acute viral replication in vivo and possibly in the reactivation process.

3T3 Cells↗
PubMed1993

Cigarette smoking, polyunsaturated fats, and coronary heart disease.

The relation between smoking habit and diet was investigated in 910 men and women. Diet was assessed by a self-administered food frequency questionnaire. After adjustment for age, sex, and occupational group, smokers had a substantially higher saturated fat (SFA) intake and much lower polyunsaturated fat (PUFA), principally due to a lower linoleic acid (LA) intake, resulting in a lower P:S ratio compared with never smokers, and these dietary differences remained after adjustment for alcohol consumption, BMI, and energy intake. Smokers also had different food choices obtaining more PUFA from saturated fat products such as dairy foods, lard, and ordinary margarine, and less from concentrated sources such as PUFA margarines and vegetable oils than nonsmokers. The food choices of cigarette smokers leading to a higher SFA and lower PUFA intakes may partly explain their increased risk of coronary heart disease.

Adult↗
PubMed1993

Comparison of a food frequency questionnaire with a 10-day weighed record in cigarette smokers.

The aim of the study was to compare nutrient intakes estimated by a self-administered food frequency questionnaire and a 10-day weighed record in 122 men and 179 women cigarette smokers aged 40-59 years. Comparison of nutrient intake by means, per cent mean differences and ability to rank individuals correctly between the methods showed good agreement for most nutrients. Spearman rank correlations were statistically significant for all nutrients except vitamin A intake in men; adjusting for energy intake increased the strength of the associations found. Bland-Altman plots showed differences in agreement over the range of intakes for energy in men and ascorbic acid in women. Food frequency questionnaires may be used to assess the dietary habits of smokers, but some caution is required and the method should be assessed in the study sample before being applied to the whole sample.

Ascorbic Acid↗
PubMed1993

Ocular and associated neuropathologic observations in suspected whiplash shaken infant syndrome. A retrospective study of 12 cases.

We examined the eyes of 12 infants who died with the clinical and pathologic diagnosis of the shaken baby syndrome. The ocular histopathologic findings and the neuropathologic findings were compared. Preretinal, intraretinal, and subretinal hemorrhages were observed; hemorrhages of the superficial retinal layers and subsensory retinal space predominated. Retinal hemorrhages were found in 12 cases, intracranial hemorrhage was found in 11 cases, and cerebral edema was found in 10 cases. The intraretinal and periretinal hemorrhages were most prevalent at the posterior pole. Five cases had retinal folds. There was a low incidence of optic disc edema and choroidal hemorrhage.

Brain Edema↗
PubMed1992

Prevention of infection in critically ill patients by selective decontamination of the digestive tract.

OBJECTIVE: To determine whether selective decontamination of the digestive tract using oral and nonabsorbable antimicrobial agents and parenteral cefotaxime prevents infection in critically ill patients. DESIGN: Randomized, controlled trial without blinding. SETTING: Surgical trauma and medical intensive care units in a tertiary referral hospital. PATIENTS: One hundred fifty patients admitted to surgical trauma and medical intensive care units during a 3-year interval, whose condition suggested a prolonged stay (greater than 3 days). INTERVENTION: Patients were randomly allocated to an experimental group (n = 75) that received cefotaxime, 1 g intravenously every 8 hours for the first 3 days only, and oral, nonabsorbable antibiotics (gentamicin, polymyxin, and nystatin by oral paste and oral liquid) for the entire stay in the intensive care unit. Control patients (n = 75) received usual care. MEASUREMENTS: The number of infections, total hospital days, and deaths, as well as the number of days in intensive care unit, were recorded. RESULTS: Control patients experienced more infections (36 compared with 12, P = 0.04), including bacteremias (14 compared with 4, P = 0.05) and pulmonary infections (14 compared with 4, P = 0.03). Although total hospital days, days in intensive care, and the overall death rate all were lower in the treatment group, these differences were not statistically significant. Clinically important complications of selective decontamination of the digestive tract were not encountered. CONCLUSIONS: Selective decontamination of the digestive tract decreases subsequent infection rates, especially by gram-negative bacilli, in selected patients during long-term stays in the intensive care unit.

Administration, Oral↗